Our objective is to determine the physiological role of vasoactive intestinal peptide (VIP) as a local (i.e., paracrine and/or neurocrine) regulatory peptide. The location of VIP in the gut determines the tissues studied. Gastric secretory and endocrine function will be studied in isolated gastric tubules and antral slices, respectively and colonic secretion in isolated goblet and columnar cells. The role of VIP as a peptidergic neurotransmitter will be studied in isolated smooth muscle cells of the gut. The use of isolated cells should define the specificity of the action of VIP and its interaction with other regulatory agents at cellular level. The role of VIP in the regulation of exocrine and endocrine pancreatic function will be examined in the vascularly perfused pancreas which maintains the unique insulo-acinar vascular system in this organ. Although the liver is normally devoid of VIP, high concentrations can reach it from the portal circulation in cases of VIP-secreting tumors: studies in cultured liver cells will examine the effect of VIP on glycogen metabolism.